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M9470042.TXT
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1994-07-02
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Document 0042
DOCN M9470042
TI Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag
variants [see comments]
DT 9409
AU Klenerman P; Rowland-Jones S; McAdam S; Edwards J; Daenke S; Lalloo D;
Koppe B; Rosenberg W; Boyd D; Edwards A; et al; Nuffield Department of
Clinical Medicine, University of Oxford,; UK.
SO Nature. 1994 Jun 2;369(6479):403-7. Unique Identifier : AIDSLINE
MED/94255016
CM Comment in: Nature 1994 Jun 2;369(6479):355
AB Most asymptomatic individuals infected with HIV-1 have a cytotoxic T
lymphocyte (CTL) response to the virus Gag proteins which can be
demonstrated in vitro. Epitopes have been mapped in p17 Gag and p24 Gag
restricted by HLA-B8 (p17-3 and p24-13) and B27 (p24-14). Viruses
isolated from patients who make CTL responses to these peptides vary
within the genetic sequences encoding these epitopes and some mutations
lead to reduction in killing activity in vitro. This was attributed to
either failure of the variant epitope to bind major histocompatibility
complex class I or failure of T-cell receptors to bind the presented
peptide. But peptide variants of class I-restricted epitopes cause
'antagonism', that is, the presence of a variant epitope (in the form of
peptide) inhibits normal lysis of targets presenting the original
epitope. This mirrors similar findings in class II-restricted systems.
Here we report that naturally occurring variant forms of p17-3, p24-13
and p24-14 may cause antagonism of CTL lines derived from the same
individuals. The effect is present if the epitopes are derived from
synthetic peptides and when they are processed from full-length proteins
expressed by either recombinant vaccinia constructs or replicating HIV.
DE Amino Acid Sequence Antigenic Determinants/GENETICS/IMMUNOLOGY Cell
Line Gene Products, gag/GENETICS/*IMMUNOLOGY Human HIV
Antigens/GENETICS/IMMUNOLOGY HIV Core Protein p24/GENETICS/IMMUNOLOGY
HIV-1/*IMMUNOLOGY HLA-B8 Antigen/IMMUNOLOGY Molecular Sequence Data
Peptide Fragments/CHEMICAL SYNTHESIS/GENETICS/IMMUNOLOGY Receptors,
Antigen, T-Cell/*ANTAGONISTS & INHIB/IMMUNOLOGY Recombinant
Proteins/GENETICS/IMMUNOLOGY Support, Non-U.S. Gov't T-Lymphocytes,
Cytotoxic/*IMMUNOLOGY Vaccinia Virus/GENETICS Variation (Genetics)
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).